This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Higher susceptibility of the elderly to infectious diseases is associated with an age-related waning of immunity, termed immune senescence, which remains incompletely understood. This program project grant aims to define a sophisticated model of human immune aging in Rhesus macaques (RM), and apply this model to elucidate the mechanisms of underlying immune senescence. The overarching program hypotheses are that: 1) RM will provide an outstanding model for human immune senescence: and 2) immune aging is the composite result of changes in multiple interactive components of the immune system [T-cells, B-cells, dendritic cells (DC) and their interaction with environment (e.g., persisting infections)]. These studies will test the above hypotheses by assessing the evolution of, and mechanisms responsible for, immune senescence in RM. The Program contains four projects that will study age-related changes in: 1) DC immunity;2) humoral immunity;3) cellular immunity to new antigens;and 4) cellular immunity to persistent infection and reinfection. Long-term goals are to use these findings to improve protective immunity in old RM, and subsequently, elderly humans.